Abstracts

To investigate the safety and efficacy of zonisamide (ZNS), a broad-spectrum antiepilepsy drug licensed in the United States and Japan and under development in Europe, as adjunctive treatment for refractory localization-related epilepsy. A total of 351 patients with inadequately controlled partial seizures with or without secondary generalization were randomized to placebo, ZNS 100 , 300, or 500 mg/d (2:1:1:2) in a double-blind trial. An upward dose-titration period ([ge]6 weeks) was followed by an 18-week fixed-dose assessment phase. Primary efficacy outcomes were the differences between ZNS 500 mg/d and placebo in the change in frequency of complex partial seizures (CPS) from baseline and in the proportion of CPS responders (ie, patients with a [ge]50% seizure frequency decrease from baseline). Tolerability was also assessed during the study. ZNS 500 mg/d significantly reduced CPS frequency compared with placebo (by [ndash]51.2% vs [ndash]16.3%, respectively; P[lt].0001) and resulted in a significantly higher proportion of CPS responders (52.3% vs 21.3%, respectively; P[lt].001). Both ZNS 500 mg/d (P[lt].0001) and 300 mg/d (P=.0005) were statistically superior to placebo in reducing the frequency of all seizures. Responder rates for all seizures showed a significant (P[lt].0001) linear dose-response relationship, with 52.5%, 42.2%, 29.6%, and 17.9% of patients responding to ZNS 500 mg/d, 300 mg/d, 100 mg/d, and placebo, respectively. ZNS was well tolerated overall, with serious treatment-emergent adverse events occurring in a similar proportion of patients receiving ZNS 500 mg/d (7.6%), 300 mg/d (9.1%), and placebo (8.3%). ZNS is a dose-dependent, effective, and well-tolerated adjunctive therapy for patients with refractory localization-related epilepsy. (Supported by Eisai Inc.)